Miyahara Koji, Nouso Kazuhiro, Dohi Chihiro, Morimoto Yuki, Kinugasa Hideaki, Wada Nozomu, Takeuchi Yasuto, Kuwaki Kenji, Onishi Hideki, Ikeda Fusao, Miyake Yasuhiro, Nakamura Shinichiro, Shiraha Hidenori, Takaki Akinobu, Amano Maho, Nishimura Shin-Ichiro, Yamamoto Kazuhide
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hepatol Res. 2015 Sep;45(9):986-993. doi: 10.1111/hepr.12441. Epub 2015 Jan 13.
Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application.
We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters.
The total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3 cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC.
We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.
在包括肝细胞癌（HCC）在内的癌症中报道的大多数N-糖基化修饰是基于对少数患者或特定蛋白质的检测。本研究的目的是系统地揭示肝癌发生过程中全血清N-聚糖谱的变化，并阐明其临床应用。
我们分析了105例慢性肝炎/肝硬化（CH/LC）患者、年龄和性别匹配的健康志愿者（HLT）以及114例HCC患者的血清。通过一种新的、定量的、高通量方法全面测量血清N-聚糖谱，并与临床参数进行比较。
CH/LC患者的N-聚糖表达总量显著高于HLT患者；然而，CH/LC患者和HCC患者之间未观察到差异。在HCC患者中，与CH/LC患者相比，带有岩藻糖残基的多天线聚糖，特别是m/z 3195增加。m/z 3195的表达较高，尤其是在肝内病变数量较多（>3个）、肿瘤体积较大（>3 cm）、有肉眼可见的血管侵犯或转移的患者中。生物合成途径同一路径上的聚糖对比例（m/z 3195/1914）在区分HCC和CH/LC方面显示出比任何其他单一聚糖更高的受试者操作特征曲线下面积，为0.810。
我们全面展示了肝病患者血清N-聚糖变化的全貌，并阐明了聚糖作为肝病进展新生物标志物的可能用途。
